Revealing new treatment targets
Multiple myeloma is an incurable cancer of the antibody-producing cells called plasma cells. Malignant plasma cells as well as inflitrating the bone marrow and other organs they also activate bone-resorbing cells called osteoclasts. Activated osteoclasts in turn lead to bone destruction.
The growth of myeloma plasma cells in part depends on genes that acquire DNA changes called mutations. Such mutated genes are increasingly recognised by the ongoing cancer sequencing efforts. We propose to identify genes which although not mutated, they are important for myeloma plasma cell growth and survival.
In addition, we will investigate how a group of proteins, call BET proteins, involved in the reading of the epigenetic code, are involved in the activation of osteoclasts by malignant plasma cells and how a novel drug called I-BET762 that inhibits BET proteins might be useful for the treatment of destructive bone disease in myeloma.
Overall, we expect that our proposed work will provide novel insights into what sustains growth of myeloma plasma cells and will reveal new treatment targets.